9548. Topotecan

Nomenclature

CAS number: 123948-87-8
(4S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 9-[(dimethylamino)methyl]-10-hydroxy-(20S)-camptothecin; hycamptamine; SKF-104864.
C23H23N3O5; mol wt 421.45.
C 65.55%, H 5.50%, N 9.97%, O 18.98%.

Description and references

DNA topoisomerase I inhibitor; semisynthetic analog of camptothecin, q.v. Prepn: J. C. Boehm et al., EP 321122; eidem, US 5004758 (1989, 1991 both to SmithKline Beecham); W. D. Kingsbury et al., J. Med. Chem. 34, 98 (1991). HPLC determn in plasma: J. H. Beijnen et al., J. Pharm. Biomed. Anal. 8, 789 (1990). Clinical pharmacology: E. K. Rowinsky et al., J. Clin. Oncol. 10, 647 (1992); and pharmacokinetics: L. J. C. van Warmerdam et al., Cancer Chemother. Pharmacol. 38, 254 (1996). Clinical evaluation in ovarian cancer: A. P. Kudelka et al., J. Clin. Oncol. 14, 1552 (1996); in small cell lung cancer: J. H. Schiller et al., ibid. 2345. Review of clinical toxicity: K. Seiter, Expert Opin. Drug Saf. 4, 45-53 (2005); of clinical evaluation in cervical cancer as single and combination therapy: L. M. Randall-Whitis, B. J. Monk, Expert Opin. Pharmacother. 8, 227-236 (2007).

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 119413-54-6
NSC-609669; SKF-104864A; Hycamtin (GSK).
C23H23N3O5.HCl; mol wt 457.91.
C 60.33%, H 5.28%, N 9.18%, O 17.47%, Cl 7.74%.

Properties

Light yellow to greenish powder, mp 213-218° (dec). Soluble in water up to 1 mg/ml. Hygroscopic. Heat and light sensitive.

Therapeutic Category

Antineoplastic.

Keywords

Antineoplastic; Alkaloids/Natural Products; Camptothecin Derivatives; Topoisomerase I Inhibitor